Tolerance to nicotine develops with chronic smoking and may be associated with the onset of tobacco dependence. It is unclear how quickly this tolerance dissipates after terminating exposure to nicotine. We propose to longitudinally assess responses to measured doses of nicotine by nasal spray in 30 male and female smokers as they smoke ad lib for 2 days (baseline), quit for 6 days, and then resume smoking for 2 days on the CRC. We hypothesize that responses to nicotine will become larger over the 6 days of cessation.